title: Tissue factor expressed by microparticles is associated with mortality but not with thrombosis in cancer patients.
abstract: A prothrombotic state is one of the hallmarks of malignancy and a major contributor to morbidity and mortality in cancer patients.Tissue factor (TF) is often overexpressed in malignancy and is a prime candidate in predicting the hypercoagulable state. Moreover, increased number of TF-exposing microparticles (MPs) in cancer patients may contribute to venous thromboembolism (VTE). We have conducted a prospective cohort study to determine whether elevated TF antigen, TF activity and TF associated to MPs (MPs-TF) are predictive of VTE and mortality in cancer patients. The studied population consisted of 252 cancer patients and 36 healthy controls. TF antigen and activity and MPs-TF were determined by ELISA and chromogenic assays. During a median follow-up of 10 months, 40 thrombotic events were recorded in 34 patients (13.5%), and 73 patients (28.9%) died. TF antigen and activity were significantly higher in patients than in controls (p<0.01) mainly in patients with advanced stages, whereas no differences were observed for TF activity of isolated MPs. We did not find a statistically significant association of TF variables with the risk of VTE. Multivariate analysis adjusting for age, sex, type of cancer and other confounding variables showed that TF activity (p<0.01) and MPs-TF activity (p<0.05) were independently associated with mortality. In conclusion, while TF variables were not associated with future VTE in cancer patients, we found a strong association of TF and MPs-TF activity with mortality, thus suggesting they might be good prognostic markers in cancer patients.
authors.affiliation: José A. Páramo, Servicio de Hematología, Clínica Universidad de Navarra, Av. Pio XII, 36, 31008 Pamplona, Navarra, Spain, Tel.: +34 948 296397, Fax: +34 948 296500, E-mail: japaramo@unav.es.
authors.forename: C
authors.initials: C
authors.lastname: Hernández
authors.forename: J
authors.initials: J
authors.lastname: Orbe
authors.forename: C
authors.initials: C
authors.lastname: Roncal
authors.forename: M
authors.initials: M
authors.lastname: Alvarez-Hernandez
authors.forename: S
authors.initials: S
authors.lastname: Martinez de Lizarrondo
authors.forename: M T
authors.initials: MT
authors.lastname: Alves
authors.forename: J
authors.initials: J
authors.lastname: García Mata
authors.forename: J A
authors.initials: JA
authors.lastname: Páramo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles; D003029:Coagulants / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000401:mortality*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism*; D013997:Time Factors; D054556:Venous Thromboembolism / Q000378:metabolism*
chemical_list: D003029:Coagulants; D013925:Thromboplastin